This invention relates to glucose monitoring by means of an implantable sensor module having a transcutaneous telemetering ability.
Diabetes mellitus is treated with injections of insulin in order to counter the inability of the pancreas to manufacture and secrete insulin in response to elevated glucose levels. For this treatment to be effective, it is necessary to be able to monitor the glucose concentration in the body so as to specify the appropriate amount and time of administration of insulin. This requires a device for measuring glucose levels in the body. Thus, considerable research has been expended to develop an effective implantable glucose sensor.
A considerable number of implantable glucose sensors are premised on the so-called "enzyme electrode." The enzyme electrode consists of an immobilized enzyme that catalyzes a chemical reaction involving glucose and oxygen which can be readily monitored. Generally, the enzymatic reaction involves the catalytic conversion of glucose to gluconic acid with simultaneous consumption of oxygen. The enzyme responsible for this action is glucose oxidase. The decrease in oxygen is measured by an amperometric oxygen electrode.
Several implantable glucose sensors are presently available. For example, Bessman et al. in U.S. Pat. No. 4,431,004 describes a method and apparatus for determining glucose content by sensing the absolute level of oxygen concentration in the blood, and correcting the output differential measurement indicative of the glucose content according to the absolute level of oxygen. In addition, the Bessman et al. device compensates for temperature fluctuations in the body by having a thermistor included in the electrosystem. U.S. Pat. No. 4,458,686 of Clark describes a subcutaneous method of measuring glucose in bodily fluids. Glucose oxidase is injected beneath the dermis where it reacts with glucose, and in the process consumes oxygen. The resulting decrease in oxygen is sensed by a transcutaneous electrode placed over or near the injection site. The byproducts of the catalytic reaction, gluconic acid and hydrogen peroxide diffuse away from the site, and then are removed by the blood stream.
In addition to the implantable glucose sensors mentioned above, there also exist several devices that are suitable for detecting glucose in vitro, but have severe limitations when used in vivo. For example, Hicks et al. U.S. Pat. No. 3,542,662 describes a dual electrode system having an enzyme-containing membrane disposed between a fluid bead assay and a first oxygen sensor electrode, and a similar membrane not containing enzymes disposed between a fluid and second reference electrode. Oxygen diffuses through the enzyme-containing membrane and is consumed in an equal molar reaction with glucose catalyzed by glucose oxidase. Consequently, oxygen is unavailable for detection by the oxygen sensor electrode. The second oxygen sensor electrode measures the concentration of oxygen existing in the absence of the enzyme-catalyzed reaction. Thus, the difference in oxygen levels detected by the two electrodes is proportional to the glucose concentration. While this sensor works adequately in vitro, in vivo the device is unreliable in that it does not function adequately in low-oxygen environments.
At present there does not exist an implantable glucose sensor suitable for detecting glucose in regions of the body where oxygen concentrations are lower than glucose concentrations. However, Fisher and Abel in "A Membrane Combination for Implantable Glucose Sensors, Measurements in Undiluted Biological Fluids" (Trans. Am. Soc. Artif. Intern. Organs, Volume XXVIII, 1982), have approached the problem by fabricating an oxygen electrode sensor that has disposed about its working face a hydrophobic layer in contact with an enzyme layer. The hydrophobic layer has a minute hole that is aligned with the oxygen electrode sensor beneath it so as to allow predominantly access of glucose to contact the enzyme layer directly above the oxygen electrode. The hydrophobic layer is composed of material that is predominantly permeable to oxygen, and not glucose. Thus, oxygen diffuses into the enzyme layer at all points across the surface of the hydrophobic layer whereas glucose diffuses in only through the hole in the hydrophobic layer. While this design effectively establishes a stoichiometric excess of oxygen over glucose in a region of the enzyme layer, it has several unattractive features. First the small amount of enzyme disposed for action on glucose entering the minute hole tends to become inactivated in a relatively short time. Moreover, because glucose entry is restricted to a hole in the hydrophobic membrane, the range of glucose concentrations detectable is narrow.
An additional desirable feature of a glucose monitoring system that is not presently available is a telemetry capability that would transcutaneously transmit data relevant to the glucose levels present in the body to an apparatus outside the body capable of continuously monitoring the user's status.
Transcutaneous telemetry systems having implantable electrode modules are known in the art. For example, there are pacemakers available which, when implanted and connected to the heart, can monitor electrocardial activity through electrodes attached to the pacemakers. The electrodes function as electropotential sensors, and the pacemakers include interface circuitry which buffers the sensor signals, formats them, and transmits the formatted signals by way of a bi-directional RF communication link to an external communication module. The telemetered signals are monitored and processed through the external module.
Further, it is known in the art to provide for enablement of two or more functions within implanted devices. For example, the implantable pacemakers can be programmed to switch electrode functions from passive electrocardial monitoring to active electrical stimulation. The switching of function can be implemented by means of a command transmitted to the implanted device from the external module via the RF link. Programmable circuitry in the implanted device alters electrode function in response to the commands. In this regard, see U.S. Pat. No. 4,550,732 of Batty, Jr. et al. and U.S. Pat. No. 4,571,589 of Slocum et al.
However, at present, there are no systems that include the means to transcutaneously monitor physiochemical processes in the body. Such systems would be very useful in the glucose-monitoring example given above.